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J line jointer5/4/2023 The phase III MAGNITUDE study was designed to compare the efficacy and safety of niraparib + AAP versus placebo + AAP for first-line mCRPC. Given the pharmacokinetic results and safety profile, 200-mg niraparib was chosen to be combined with AAP for future studies. When the 300-mg dose of niraparib was combined with AAP, three of eight patients experienced DLT. 1 The daily combination dose of niraparib in combination with AA was established as 200/1,000 mg, respectively, plus prednisone on the basis of achieving maximum concentration and area under the curve values within the efficacious target combination ranges, with no dose-limiting toxicities (DLTs) observed in the phase Ib BEDIVERE study. 18 Abiraterone acetate (AA) plus prednisone (AAP) is a standard first-line therapy that improves progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. 13- 17 In the phase II GALAHAD trial ( identifier: NCT02854436), an objective response rate (ORR) of 34.2% with niraparib monotherapy as third-line or higher therapy was achieved in patients with mCRPC, measurable metastases, and BRCA1/ 2 pathogenic alterations. Niraparib, a potent and highly selective inhibitor of PARP-1 and PARP-2, is approved in the United States, Canada, Europe, and China in select patients for several indications, including ovarian, fallopian tube, and primary peritoneal cancers. *Relevance section written by JCO Associate Editor Michael A. These results underscore the need for HRR gene testing for metastatic prostate cancer and support the use of niraparib + AAP as first-line combination therapy for these patients with particularly poor prognoses.* Such results underscore the need for HRR gene testing for metastatic prostate cancer and support the use of niraparib + AAP as first-line combination therapy for these patients with particularly poor prognoses. Patients with mCRPC and HRR alterations experienced substantial and clinically meaningful benefit from the combination of niraparib + AAP, with no new safety signals that affected the benefit-risk profile. The phase III MAGNITUDE study prospectively enrolled patients into two cohorts on the basis of HRR biomarker status and compared the efficacy and safety of niraparib and abiraterone acetate plus prednisone (niraparib + AAP) versus placebo + AAP as first-line treatment for patients with mCRPC. Metastatic castration-resistant prostate cancer (mCRPC) with alterations in homologous recombination repair (HRR)–associated genes has been associated with poor prognosis and resistance to current systemic therapies. Vozianov Institute of Urology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraineġ4Janssen Research & Development, LLC, Spring House, PAġ5Janssen Research & Development, LLC, Raritan, NJġ6Janssen Research & Development, LLC, Los Angeles, CAġ7Janssen Research & Development, LLC, Titusville, NJġ8Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia On behalf of the MAGNITUDE Principal Investigators Show MoreġBC Cancer – Vancouver Center, University of British Columbia, Vancouver, BC, CanadaĢMemorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NYģMassachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MAĤHouston Methodist Cancer Center, Houston, TXĦDepartment of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, SpainħDepartment of Urology Cancer Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South KoreaĨHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CAĩLiga Norte Riograndense Contra o Câncer, Natal, Brazilġ0Department of Medical Oncology, Institut Bergonié, Bordeaux, Franceġ1Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysiaġ2Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Polandġ3Kyiv City Clinical Oncology Center and Academician O.F.
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